Renal Control of Acid-Base Balance Flashcards
Why must pH stay at 7.4?
- some AA have net positive charge or net negative charge at this ph
- any changes will impact electrostatic charge needed for proper protein folding, alters protein -protein interaction, drug binding/ability to enter cells, etc
Which metabolic acid sources are used for volatile purposes?
- where in body
Glucose + O2 -> H+ + HCO3-
Fat + O2 -> H+ + HCO3-
in Lungs (24,000 mEq/ day)
Which metabolic acid sources are used for fixed (nonvolatile) purposes?
- where in body
Glucose (anaerobic) -> H+ + lactate
Cysteine + O2 -> H+ + sulfate
Phosphoprotein + O2-> H+ + phosphate
kidneys
(50 mEq/day)
Meaning of Pk
pH at which this buffer, acting as “H+ sponge” has sopped up half of the H+ it can hold
Ph of gastric HCl
0.8
HCO3-/ H2CO3
- name buffer system
- pK value
- Reaction equation
bicarbonate
6.1
H+ + HCO3- <=> H2O + CO2
Hb-/ HHb
- name buffer system
- pK value
- Reaction equation
hemoglobin
7.3
HHb <=> H+ + Hb-
HPO4/ H2PO4
- name buffer system
- pK value
- Reaction equation
Phosphate
6.8
H2PO4 <=> H + HPO4-
Pr-/ HPr
- name buffer system
- pK value
- Reaction equation
plasma proteins
6.7
HPr <=> H+ + Pr-
Four buffer pairs in body buffer system
- what is their rates
1) HCO3/ H2CO3
2) Hb-/ HHb
3) HPO4/ H2PO4
4) Pr-/ HPr
ALL instantaneous
Organs in Body Buffer System (4)
- list mechanism
1) Lungs
- regulates retention/ elimination of CO2 and H2CO3
2) Ionic Shifts
- exchange of intracellular K and Na for hydrogen
3) Kidneys
- bicarbonate reabsorption/regeneration, ammonia formation, phosphate buffering
4) Bone
- exchange of calcium, phosphate, release of carbonate
Buffering of Hydrogen Ion by Plasma Proteins and Hemoglobin
- how does H+ enter body for buffering?
- transport
CO2 enter tissues
3 ways of CO2 breakdown in RBC:
a) CO2 dissolved
b) CO2 + H2O <=> H2CO3 <=> HCO3- + H+
c) CO2 + Protein -NH2 <=> Protein + H+
HCO3- + H+
- will use HCO3-/Cl- transport to bring Cl- in , HCO3- out of RBC
Volume of K in ICF? ECF
ICF= 140 mM k+ ECF= 4.0 mM K+
If ECF is in acidemia, what will happen in ICF?
ICF takes in H+
= low ECF pH ( <7.35)
= high H+, buffered by raising ECF K+
If ECF is in alkalemia, what will happen in ICF?
ICF donates H+
= high ECF pH (>7.45)
= low H, buffered by lowering ECF K
Henderson-Hasselbalch Equation
- which part of equation is controlled by kidneys? lungs?
ph= 6.1 + Log [HCO3-]/ [H2CO3]
or
ph= 6.1 + Log [HCO3-]/ (0.03 x PCO2)
[HCO3-]= controlled by kidneys, slow with large capacity
[H2CO3]= controlled by lungs, fast with limited capacity
Ventilatory Rate effect on pH
- hyperventilation? hypoventilation?
Hyperventilation= less CO2= less H2Co3= less H= high pH
Hypoventilation= more CO2= more H2Co3= more H= low pH
Renal Reabsorption of Bicarbonate (%)
- PT
- Thick LOH
- CD
in Glomerulus : 4320 mEq/ Day
- PT: 85% , 3672 mEq/ day
- Thick LOH: 10%, 432 mEq/day
- CD: 4.9%, 215 mEq/day
Detailed Reabsorption of filtered bicarbonate by Proximal Tubule
- transports on apical side
- transports on basolateral side
Apical side
- Na/H exchange ( Na in , H+ out of tubular fluid)
- H ATPase
- Bicarbonate -> H2O + Co2 enter cell via carbonic anahydrase
Basolateral side
- Na/K Atpas
- Na/ HCo3- co transport (out)
- HCO3-/ Cl- ( HCO3 out into blood)
What factors increase H+ secretion?
- Primary (2) / location
- Secondary (5)/ location
Primary (entire nephron)
1) decrease plasma HCO3- (decrease pH)
2) Increase in partial pressure at arterial carbon dioxide
Secondary (all are in PT except #4 is CD)
1) increased in HCO3- filtered load
2) decrease ECF volume
3) increase Ang II
4) increase aldosterone
5) Hypokalemia
What increased during hypokalemia?
why?
- what transporters are involved?
ammonia genesis and net acid secretion increased
- intracellular acidifcation
- hormones upregulates ammoniagenesis genes to increase NH4+ excretion and decrease K+ secretion
- renal glutamin transporter SN1
- mitochondrial glutaminase (GA)
- glutamate dehydrogenase (GDH)
What factors decrease H+ secretion?
- Primary (2) / location
- Secondary (5)/ location
- when is hyperkalemia relevant
Primary (entire nephron)
1) increase plasma HCO3- (increase pH)
2) decrease in partial pressure at arterial carbon dioxide
Secondary (all are in PT except #3 is CD)
1) decreased in HCO3- filtered load
2) increase ECF volume
3) decrease aldosterone
4) Hyperkalemia
- during type IV renal tubular acidosis
Phosphate buffering of secreted hydrogen ions
- what transports are on apical side?
- what transports are on basolateral side?
- what is pathway for Na
- regenerates the plasma HCO3- that had been “consumed” elsewhere when NaH2PO4 lost an H= in acid body
- H+ into urine
Basolater side
- Na/K ATPase
- passive diffusion for HCO3 and CO2
Apical side
- Na/H exchange ( H out into tubular lumen)
NaHPo4- (from tubular lumen) -> NaHPo4 + H+ -> NaH2PO4 -> carries H into the lumen
How ammonia in nephron generate new Bicarbonate
- in proximal tubule
- in collecting duct
significance
PT
- Glutamine in lumen-> breakdown to ammonia (x2) -> NH3 goes out into tubular fluid -> combine with H+ -> form NH4
-NH3 reabsorbs in tubular fluid
CD
- CO2 + H2O -> H2CO3 via CA-> breaks down into HCO3 + H
HCO3 -> reabsorbs into blood
H+ ->enters tubular fluid into CD
H+ combines with NH3 to become NH4 and excreted into urine
- uses Na/K/2CL transporter
NH4 replaces K in this transporter - diffuses into CD where it is ion trapped
Reabsorption and secretion of bicarbonate in Alpha intercalated cells
- transporter on apical side
- transporter on basolateral side
- significance
- secretes H
- Reabsorbs HCO3-
apical side
- K/H ATPase ( K in )
- H ATPase ( H out)
basolateral membrane
- HCO3/ Cl- antiporter (HCO3 in)
- “new” bicarbonate is generated during process of urinary acidification when secreted H+ is buffered by NH3-> NH4+, phosphate for excretion while bicarbonate is reabsorbed
Reabsorption and secretion of bicarbonate in Beta intercalated cells
- transporter on apical side
- transporter on basolateral side
- reabsorbs H+
- secretes HCO3-
Apical Side
- HCO3/ Cl- antiporter (HCO3 in tubular fluid)
Basal Side
- H+ Atpase ( H into blood)
Net Acid Excretion Equaion
- what must it equal?
NA= (U(nh4) x V) + (U (Ta) x V) - (U (HCO3) x V)
- NAE must equal nonvolatile acid production each day in order to maintain acid-base balance
Titratable Acids
salts of primarily phosphate, sometimes creatinine
~ 1/3 NAE
Ammonium ( Nh4+)
synthesis and secretion is responsible for ~2/3 NAE
-body can easily make as much as needed
Why is ammonium is not measured as about of titratable acidity?
high pK of ammonium means no H is removed from NH4 during titration to a ph of 7.4
Normal Values of Acid- Base Disturbances
- ph
- H+
- Pco2
- HCO3-
ph= 7.4
H+= 40 mEq/L
PCO2= 40 mmHg
HCo3-= 24 mEq/L
Respiratory Acidosis
- ph
- H+
- Pco2
- HCO3-
- decrease ph
- increase H+
- increase Pco2
- increase HCO3-
Respiratory Alkalosis
- ph
- H+
- Pco2
- HCO3-
- increase ph
- decrease H+
- decrease Pco2
- decrease HCO3-
Metabolic Acidosis
- ph
- H+
- Pco2
- HCO3-
- decrease ph
- increase H+
- decrease Pco2
- decrease HCO3-
Metabolic alkalosis
- ph
- H+
- Pco2
- HCO3-
- increase ph
- decrease H+
- increase Pco2
- increase HCO3-
Metabolic Acidosis with compensation and correction
- pathway
Renal
low serum ph-> increased acid titration -> increase ammonium and H2PO4-> increase acid excretion in urine-> increase bicarbonate regeneration -> increase serum ph
Respiratory
low serum ph-> hyperventilation-> decrease PCo2-> decrease CO2 + H2O-> decrease H2Co3-> decrease H
Normal Anion Gap
8-16 mEq/L
Causes of Metabolic Acidosis
- High Anion Gap (9)
- Non- Anion Gap (7)
High Anion Gap (MUDPILERS)
- Methanol
- Uremia
- DKA/ Alcoholic Ketoacidosis
- Paraldehyde ( obsolete sedative-hypnotic)
- Isoniazid (used to treat tuberculosis)
- Lactic Acidosis
- EtOH/ Ethylene Glycol
- Rhabdo/ Renal failure
- Salicylates
Non-Anion Gap (HARDUPS)
- Hyperalimentation
- Acetazolamide
- Renal Tubular Acidosis
- Diarrhea
- Uretero-Pelvic Shunt
- Post-hypocapnia
- Spironolactone
Causes of Metabolic Acidosis (3)
1) Excessive production or ingestion of fixed H+
2) loss of HCO3-
- Type 2 renal tubular acidosis ( renal loss of HCO3-)
3) Inability to excrete fixed H
- Type 1 renal tubular acidosis ( decrease excretion of H as titratable acid and NH4)
- Type 4 renal tubular acidosis ( hyperaldosteronism)
Type 1 Renal Tubular Acidosis
- location
- acidosis?
- potassium
- pathophysiology
- what does it impair
- distal tubules
- severe acidosis, normal anion gap
- hypokalemia
- failure of H+ secretion by alpha intercalated cells
- impair acid-base homeostasis and phosphate/ammonia buffer
- urinary stone formation due to hypercalciuria
- bone demineralization
Type 2 Renal Tubular Acidosis
- location
- acidosis?
- potassium
- pathophysiology
- Proximal Tubules
- acidosis
- hypokalemia
- failed HCO3- reabsorption from urine by proximal tubular cells
Type 4 Renal Tubular Acidosis
- location
- acidosis?
- potassium
- pathophysiology
- adrenal
- mild acidosis with normal anion gap
- hyperkalemia
- deficiency/ resistance to aldosterone bc psuedomypoaldosteronism or drug
- low aldosterone/ failure to respond to it
- decrease NH3 synthesis by PT
- ACE inhibitors , spironolactone can cause this
impair acid-base homeostasis
Metabolic Acidosis Symptoms
- mild
- with ph <7.10
mild acidosis- asymptomatic
with ph< 7.10 ( or higher if rapidly developed)
- nausea, vomiting, malaise
see long deep breaths at normal rate (respiratory compensation) without dyspnea
Metabolic Alkalosis with Compensation and Correction
- pathway
Renal
- high serum ph-> decrease tubular reabsorption of bicarbonate -> increase bicarbonate excretion in urine -> low serum ph
- high serum ph-> decrease acid titration -> decrease ammonium and HPO4-> decrease bicarbonate regeneration -> decrease acid excretion in urine -> low serum pH
Respiratory
- high serum ph-> hypoventilation -> increase PCO2-> increase CO2 + H2O-> increase H2Co3-> increase H+ -> low serum ph
Causes of Metabolic Alkalosis (8)
- Contraction
- Licorice
- Endo ( Conn, Cushing, Bartter)
- Vomiting
- Excess Alkali
- Refeeding Alkalosis
- Post-hypercapnia
- Diuretics
Causes of Metabolic Alkalosis
1) Loss of H (vomiting, hyperaldosteronism)
2) Gain of HCO3 (ingestion of NaHCo3)
3) Volume contraction alkalosis (loop or thiazide diuretic)
Metabolic Alkalosis Symptoms
- mild
- more severe
Mild: symptoms of underlying disorder
severe: increased binding of CA2+=> hypocalcemia
- headache, lethargy, neuromuscular excitability,
- delirium, tetany, seizures
- angina symptoms, arrhytias, weakness
Respiratory Acidosis with compensation
- pathway
decrease ventilation-> increase blood PCo2-> increase bicarbonate-> low serum ph -> renal compensation-> increased acid titration -> increase ammonium and HPO4–> increase acid excretion in urine-> increase bicarbonate regeneration-> increase serum pH
Causes of Respiratory Acidosis
- acute (4)
- chronic (2)
Acute CANS - CNS depression - Airway obstruction - Neuromuscular disorders - Sever Pneumonia, embolism, edema
Chronic
- COPD ( chronic obstructive pulmonary disease)
- anything chronic that leads to impaired ventilation
Causes of Respiratory Acidosis (4)
1) inhibition of medullary respiratory center
- opiates, barbiturates
2) disorders of respiratory muscles
- ALS
- MS
3) airway obstruction
- aspiration
- obstructive sleep apnea
- laryngospasm
4) disorders of gas exchange
- COPD
- Pneumonia
- pulmonary edema
Respiratory Acidosis Symptoms
- acute
- slowly developing, stable
acute
- headache, confusion, anxiety, drowsiness, stupor, tremors, convulsion, possible coma (CO2, narcosis)
Slowly developing, Stable (as in COPD)
- may be well tolerated
- memory loss, sleep disturbances, excessive daytime sleepiness, and personality changes
- gait disturbance, tremor, blunted deep tendon reflexes, myoclonic jerks, asterixis, papilledema
Respiratory Alkalosis with Compensation
- pathway
increased ventilation-> low blood PCo2-> decrease H+ and H2CO3-> increase serum pH-> renal compensation-> decreased acid titration-> decrease NH4 and HPO4-> decrease acid excretion in urine-> decrease bicarbonate regeneration -> low serum ph
Causes of Respiratory Alkalosis (6)
CHAMPS
- CNS Disease
- Hypoxia
- Anxiety
- Mechanical Ventilators
- Progesterone
- Salicylates/ Sepsis
Causes of Respiratory Alkalosis (3)
1) stimulation of medullary respiratory center
- neurological disorder
2) Hypoxemia
- high altitude
- pneumonia
- pulmonary embolism
- severe anemia
3) Mechanical Ventilation
Respiratory Alkalosis Symptoms
- acute
- chronic
Acute
- light headedness
- confusion
- peripheral and circumoral paresthesias
- cramps
- syncope
- tachypnea/ hyperpnea
- carpopedal spasm due to decrease hypocalcemia
Chronic
- asymptomatic
Metabolic Acidosis Equations
PaCo2= 40- (1.2 x (24-HCO3-)
PaCo2= (1.5 x HCO3) + 8 +/- 2
Metabolic Alkalosis Equation
PaCo2= 40 + (0.7 x HCO3- 24)
must be less than 20
Respiratory Acidosis Equations
Acute
HCO3- = 24 + (0.1 X (PaCo2-40))
Chronic
HCO3-= 24 + (0.4 X (PaCo2-40))
Respiratory Alkalosis Equations
Acute
HCO3- = 24 - (0.2 X (40- PaCo2))
Chronic
HCO3-= 24 - (0.5 X (40-PaCo2))
Range +/- 2
